In the past year, two lines of research yielded publications. In collaboration with Dr. Piszczek (NHLBI Biophysics Core) we have determined best-practice methods for the analysis of riboswitch-small molecule interactions with the first-principles method isothermal calorimetry. In collaboration with Dr. Schneekloth (NCI) we have combined high-throughput small molecule screening, X-ray crystallography, and structure-guided design to create synthetic ligands for the bacterial PreQ1 riboswitch. This study produced lead compounds with biochemical activity to be elaborated further, and also yielded insights into the mechanism of action of this important bacterial gene-regulatory RNA.